USP 800 Facility Upgrades and Components
USP 800 guidelines may present challenges for compounding facilities. Some facilities need infrastructural and mechanical modifications for compliance. System evaluation includes duct systems, HEPA fan filters, differential pressure standards, air monitoring, and external air exhaust equipment.
Sterile Compounding - Containment Primary Engineering Control
The C-PEC for sterile compounding should be located in a C-SEC, which may either be an ISO Class 7 buffer room and ante-room (preferred) or an unclassified containment segregated compounding area (C-SCA). If the C-PEC is placed in a C-SCA, the beyond use date (BUD) of all compounded sterile preparations (CSPs) so prepared should be limited as described in USP <797> for CSPs prepared in a SCA (USP 800, 2016).
- All C-PECs used for manipulation of sterile HDs should be externally vented (USP 800, 2016).
- If the C-SEC for sterile compounding is an ISO Class 7 buffer room, the C-SEC should be externally vented; provide 30 ACPH; and have a negative pressure between 0.01 and 0.03 inches of water column relative to adjacent areas (USP 800, 2016).
- The ISO Class 7 ante-room or non-HD buffer room should maintain a positive pressure of at least 0.02 inches of water column to all adjacent unclassified areas (USP 800, 2016).
- If the C-SEC for sterile compounding is a C-SCA, the C-SEC should be externally vented; provide 12 ACPH; and be at negative pressure between 0.01 and 0.03 inches of water column relative to adjacent areas (USP 800, 2016).
Non-sterile HD compounding
- Non-sterile HD compounding should be performed in a C-PEC that provides for personnel and environmental protection, such as a Class I BSC or a Containment Ventilated Enclosure (CVE) (USP 800, 2016).
- The C-PEC for non-sterile HD compounding should be placed in a C-SEC that is externally vented, have at least 12 ACPH, and be at negative pressure between 0.01 and 0.03 inches of water column relative to adjacent areas (USP 800, 2016).
The balance between zones of differing pressure is challenging. USP 800 requires all hazardous drug compounding occur within a primary engineering control (C-PEC). The C-PEC is a location within a containment secondary engineering control (S-PEC). In practice, an ISO Class 5 flow hood within an ISO Class 7 buffer area is generally sufficient. Direct compounding areas must segregate from all other rooms, be externally vented, and negatively pressurized for maintenance of a 0.01-0.03 inch water column. Too much negative pressure draws dirty air and particles in from adjoining spaces. Notably, the configuration and layout of in-process controls dynamically affect overall room performance. Workflow, equipment, and personnel all require consideration when testing and balancing cleanroom design variables.
All unpacking of hazardous drugs requires a neutral or negative pressure environment. Smaller healthcare organizations may not have a dedicated negative pressure cleanroom, nor the space requirements for an additional cleanroom. Modular cleanroom designs adapt for the facility, instead of customizing a facility for a cleanroom. Achieving an ISO Class 7 cleanroom required by USP 800 may require retrofitting an existing structure, thus consulting a team of architects and cleanroom engineers is ideal.
Cascading pressure systems need acute monitoring of air pressure differentials. Pressure monitoring ensures that filter resistance, fan and blower pressures, air velocity, and pressure drops are detectable and traceable. USP 800 requires a water column maintenance of 0.01-0.03 inch between cascaded pressure rooms based on compound classification. Upgrading will entail installing gauges with internal diaphragms that measure the amount of tension between two sealed regions of varying pressure.
Security & Access
USP 800 tightens access controls and expands labeling for hazardous drug storage. Air showers or other entry points may require updated software and hardware with a card reader that permits only authorized personnel.
Refrigerated Hazardous Drugs
USP 800 requires a dedicated hazardous drug storage refrigerator located in a negative or neutral pressure area.
External ventilation is a primary consideration for USP 800 outfitting. USP 800 requires a negative pressure room with external ventilation for compounding activities. A neutral or negative pressure room is required for all unpacking or storage of hazardous drugs (HDs). Installing or modifying the current system is needed for facilities that have traditionally unpacked HDs in a positive pressure environment.
The routing of new exhaust ductwork through a building already dense with electrical and HVAC is intensive. Sometimes upgrading existing infrastructure is possible, sometimes it is not. For critical cleanrooms that require more supporting space, the outcome has many variables: location within the building, square footage, structural requirements, cleanliness level, and more. Sometimes relocating a cleanroom to a new area or different floor of the building is ideal. Using crane systems for a cleanroom installation far above ground level is not unrealistic when lower level spaces complicate electrical, structural, or HVAC support.
Each ISO Class level is 10 times cleaner than the next lowest classification. Moving up one cleanroom class from an ISO Class 8 to an ISO Class 7 cleanroom requires nearly twice as much air. Air filtration and conditioning is a significant factor in operating expenses. The total square footage, the number of filters needed, humidity, and air intake temperature determine energy requirements. The efficiency of these systems is a direct relation to operating cost and a 25% cost increase is normal for each step up in classification.
Is Compounding Sterile and Nonsterile Compounds in the Same Room Allowed Under USP 800?
Yes, assuming that two laminar flow hoods assure separation during processing, USP 800 permits the coworking of both hazardous and nonhazardous drugs. Depending on the application, room configuration requires consideration, consulting a cleanroom engineer is beneficial.
Cleanroom Design Is Complex, But It Gets Less Complicated
Cleanroom construction, much like building a new facility, requires a myriad of workers, parts, materials, and design considerations. Sourcing components and supervising construction for a new facility is not something you’d ever take on by yourself. Why would building a cleanroom be any different?
CleanPro (that’s us) helps you achieve the correct pressurization differentials, ACPH and ISO classification requirements (i.e., cleanroom construction, retrofitting, HVAC, HEPA filters, temperature/humidity gauges) for each space. Our engineering team conducts preliminary research to determine what types of facility changes you will need to upgrade from USP 795 or USP 797 compliance.
What's The CleanPro Advantage?
The content provided is for informational purposes only. It does not constitute a recommendation for your facility or organization. This post serves as a general guideline and summary. At time of publication, the information is in good faith, critically reviewed, and according to the most concurrent information available. Compliance requires temporal evaluation on a case-by-case basis according to state and federal law. The content heirin, linked content, or other web content provided by Production Automation Corporation (PAC) makes no claims as to the final interpretations or implementation of regulatory documents provided by the FDA, State Board of Pharmacy, or United States Pharmacopeia (USP). For this reason, PAC provides on-staff, licensed engineers who are experts in regulatory and application compliance. They are available every business day, toll free (888) 903-0333 for consultation at no cost, no obligation.